Endocytosis, Adhesions and Cytoskeleton

Curved and flat clathrin structures in health and disease

Approximately 15% of the proteins produced in our bodies are destined for the surface of our cells. Remarkably, these surface proteins, along with the lipids forming the membrane, undergo rapid recycling, with estimates suggesting that the entire cell surface is turned over every few minutes*. Precise control of this dynamics is essential for cellular and tissue homeostasis, with disruptions linked to diseases like cancer, dementia and diabetes. 

One key process in maintaining this equilibrium is endocytosis, the mechanism by which membrane components are internalised. Organisms have evolved various endocytic pathways, all relying on actin-generated forces to facilitate internalisation. In our lab, we focus on clathrin-mediated endocytosis, the predominant route for membrane internalisation in most cells.

In addition to its role in endocytosis, the clathrin machinery also forms stable structures called flat clathrin lattices. We recently discovered that these structures are essential for the establishment of reticular adhesions.

In our lab, we aim to elucidate the interplay of clathrin structures with the actin cytoskeleton and cellular adhesions. This work enables us to apply our findings to understand disease processes and identify new therapeutic targets, especially for cancer.

To tackle these questions, we use a multidisciplinary approach combining state-of-the-art techniques in cell biology, biochemistry, and structural biology.


*Estimates vary between cell types and methods used. However, all of them put membrane turnover between less than a minute (Griesinger, JN 2002), to a few minutes (Hao, JBC 2000) up to 30-100 minutes (Mayor, JCB 1993; Anderson, Cell 1977; See also the bulk of work from Mark Bretscher). 

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